Colchicine (I, R1=R2=OMe) is an alkaloid widely used for a long time in therapy for the treatment of gout. In addition, colchicine is a very potent antiblastic agent which acts by blocking the formation of the mitotic spindle in cell division; this property has been thoroughly investigated for any antitumoral activity, and a great number of colchicine derivatives have been prepared for this purpose. Colchicine and thiocolchicine (I, R1=SMe, R2=OMe) are the starting materials useful for the preparation of a series of active drugs.
3-O-Demethyl-thiocolchicine glucoside, or thiocolchicoside (I R1=SMe, R2=β-D-O-glucosyl), is an active ingredient of remarkably important use in the pharmaceutical field, mainly in the therapy of diseases of the muscle-skeletal system. 3-O-Demethylcolchicine glucoside, or colchicoside (I R1=OMe, R2=β-D-O-glucosyl), is also known and endowed with pharmacological activities.
Therefore, efficient methods for the glycosidation of colchicine-type compounds, to facilitate the preparation of both compounds and novel derivatives for use in pharmacological research, would be important.
FR 2112131 discloses a process for the glycosidation of thiocolchicine comprising the reaction of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide with demethyl-thiocolchicine. This method is unsatisfactory due to the low yield and the time required for the lengthy and articulated process.
U.S. Pat. No. 5,777,136 describes a glycosidation process which involves the use of protected sugar fluorides, in particular protected derivatives of 1-fluoroglucose and 1-fluorofucose. The described process, in particular, is restricted to the preparation of 3-O-glucosyl or 3-O-fucosyl derivatives of colchicine and thiocolchicine. Even if the described yields are satisfactory, this method requires the preparation of suitably activated sugar derivatives, i.e. sugar fluorides, which means an additional step in the synthesis and the preparation and storage of reagents of relative stability.